Table 8

Screening tests for asymptomatic CAD in patients with diabetes mellitus

TestDescriptionKey resultsInclusion in a recent AHA guideline?
ECGResting electric activity through the cardiac cycleIn the UKPDS study, one in six patients with newly diagnosed type 2 diabetes mellitus had evidence of silent MI on the baseline surface ECG (211).
Prevalence of ECG abnormalities in patients with diabetes mellitus and no known CAD was even higher in older studies, approaching 20% (212).
UKPDS data indicate that an abnormal ECG is an independent risk factor for all-cause mortality and fatal MI in patients with diabetes mellitus (211).
Specific ECG abnormalities associated with increased risk of CVD events in cohort studies include pathological Q waves, LVH (particularly if accompanied by repolarization abnormalities), QRS prolongation, ST-segment depressions, and pathological T-wave inversions (213).
Abnormal ECG findings have been demonstrated to predict inducible ischemia (214).
Class IIa: A resting ECG is reasonable for cardiovascular risk assessment in asymptomatic adults with hypertension or diabetes mellitus (Level of Evidence C) (213).
ABIRatio of systolic blood pressure at the ankle and arm. Used as an indicator of underlying peripheral arterial diseaseA systematic review of ABI as a predictor of future CVD events demonstrated high specificity (≈93%) but very low sensitivity (16%) (215), thus limiting its utility as a screening test for CAD.Class IIa: Measurement of ABI is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (Level of Evidence B) (213).
Stress MPIRadioactive tracer (e.g., thallium-201, Tc99m sestamibi, or Tc99m tetrofosmin) uptake within the myocardium is assessed before and after stress with scintigraphy. Option for pharmacological stress (dipyridamole, adenosine, or regadenoson) in those not able to exerciseMiSAD (216):
  • • A total of 925 asymptomatic patients with type 2 diabetes mellitus underwent an ECG stress testing, which, if positive or equivocal, led to stress thallium MPI.

  • • Silent CAD prevalence 12.5% for abnormal exercise ECG and 6.4% for both abnormal ECG and MPI.

  • • Abnormal scintigraphy predicted cardiac events at 5 years (HR 5.5 [95% CI 2.4–12.3]; P < 0.001).

DIAD (217,219):
  • • In total, 1,123 patients with type 2 diabetes mellitus were enrolled from multiple centers (mean duration of diabetes mellitus, 8.5 years); 522 patients were randomized to adenosine sestamibi SPECT MPI, and 561 served as the control group and were randomized to follow-up alone.

  • • Silent ischemia prevalence = 21.5%.

  • • At 5 years of follow-up, there was no difference in the primary end point, nonfatal MI and cardiac death, between the screened and unscreened cohorts (overall annual rate 0.6%; 15 versus 17 events; HR 0.88 [95% CI 0.44–1.80]; P = 0.73).

  • • No differences in any secondary end points (unstable angina, heart failure, stroke, coronary revascularization).

DYNAMIT trial (218):
  • • Prospective, randomized, double-blind, multicenter study conducted in France.

  • • In total, 631 patients were randomized to either CAD screening with either a stress ETT or dipyridamole SPECT MPI versus follow-up only (without screening).

  • • Study was stopped prematurely; no difference in cardiac outcomes was seen between screened and unscreened groups (HR 1.00 [95% CI 0.59–1.71]).

Class IIb: Stress MPI may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes mellitus or asymptomatic adults with a strong family history of CHD or when previous risk assessment testing suggests a high risk of CHD (e.g., a CAC score of ≥400) (Level of Evidence C) (213).
Class III: No benefit. Stress MPI is not indicated for cardiovascular risk assessment in low- or intermediate-risk asymptomatic adults (Level of Evidence C) (213).
CAC scoringQuantitative assessment of calcium deposited within the coronary arteries (as a marker of atherosclerosis) via EBCT or multidetector CT, stratified by Agatston units, yielding CAC scores of <100 (low risk), 100–400 (moderate risk), and >400 (high risk)Linear relationship between CAC and clinical CHD events among individuals with and without diabetes mellitus (220225).
Patients with diabetes mellitus have a greater prevalence and extent of CAC than those without diabetes mellitus (225228).
Prognostic significance of elevated CAC in predicting adverse events is greater in patients with diabetes mellitus than in those without diabetes mellitus (229).
No dedicated randomized trials have suggested that the detection of subclinical CAD by CAC leads to improvement in clinical events. This represents an important area of future research.
In asymptomatic adults with diabetes mellitus ≥40 years of age, measurement of CAC is reasonable for cardiovascular risk assessment (Level of Evidence B) (213).
  • ABI, ankle-brachial index; EBCT, electron-beam computed tomography; ETT, exercise tolerance testing; LVH, left ventricular hypertrophy; MPI, myocardial perfusion imaging; SPECT, single-photon emission computed tomography.